Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder)When an Optimal Dose is Taken With Varied Carbohydrate Intake

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

TI Inhalation Powder and Humalog (Amendment 1)

TI Inhalation Powder (original protocol)

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Clinical diagnoses of type 1 or type 2 diabetes mellitus
Fasting Plasma Glucose (FPG) 80, 140 mg/dL and glycated hemoglobin (A1C) > 6.5% and < or = 10.0%.
Body mass index (BMI) of < or = 40 kg/m2
Non-smokers (never smoked or former smokers [= 6 months since cessation]) and a urine cotinine level < or = 100 ng/dL
Forced expiratory volume in 1 second (FEV1) = 70% Third National Health and Nutrition Examination Survey (NHANES III) Predicted; pre-bronchodilator FEV1 as a percentage of forced vital capacity (FEV1/Forced vital capacity(FVC)) = 70%
For subjects with type 2 diabetes mellitus: Currently receiving oral diabetic treatment or basal insulin +/- oral diabetic treatment

Exclusion Criteria:

History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, and/or any other clinically important pulmonary disease confirmed by pulmonary function test (PFT) and/or radiologic findings
Elevated liver function test (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times the normal reference range or bilirubin > 1.5 times the reference range)
Previous use of Exubera; use of Symlin (pramlintide acetate) and/or Byetta (exenatide) within the past 12 weeks
Unstable diabetes control and evidence of severe complications of diabetes mellitus (ie, autonomic neuropathy)
Exposure to any investigational product(s) in the past 12 weeks
For subjects with type 2 diabetes mellitus: In subjects taking metformin, serum creatinine > 1.4 mg/dL in female subjects and > 1.5 mg/dL in male subjects

Sites / Locations

Sansum Medical Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

TI Inhalation Powder (original protocol)

TI Inhalation Powder and Humalog (Amendment 1)

Arm Description

Under the original protocol, subjects with Type 1 and Type 2 diabetes will have TI Inhalation Powder administered prandially during dose optimization visits and meal challenge visits (with meals of varying carbohydrate contents). Subjects with Type 2 diabetes will also use TI Inhalation Powder daily at each meal between visits.

Under Amendment 1, TI Inhalation Powder will be administered prandially to a new subset of subjects with Type 2 diabetes during TI dose optimization visits and TI meal challenge visits (with meals of varying carbohydrate contents). Subjects will be crossed over to administration of Humalog 15 minutes before meals during Humalog dose optimization visits and Humalog meal challenge visits (with meals of varying carbohydrate contents). Subjects will also use TI Inhalation Powder daily at each meal between visits.

Outcomes

Primary Outcome Measures

Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects)

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

Breakfast Plasma Glucose Time 0 Corrected AUC(0-240) - Original Protocol (TI Treated Type 1 Subjects)

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

Lunch Plasma Glucose Excursion - Original Protocol (TI Treated Type 1 Subjects)

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at lunch

Breakfast Plasma Glucose Excursion - Original Protocol (TI Treated - Type 1 Subjects)

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at breakfast

Lunch Plasma Glucose Excursion - Amendment 1 ( TI Treated Type 2 Subjects)

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch

Lunch Plasma Glucose Excursion - Amendment 1 (Humalog Treated Type 2 Subjects)

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch

Secondary Outcome Measures

Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects)

Area over the plasma glucose - time curve from time 0 (immediately before starting lunch) to 240 minutes after the start of the lunch

Breakfast Plasma Glucose AOC(0-240) - Original Protocol (TI Treated Type 1 Subjects)

Breakfast area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of breakfast

Lunch Plasma Glucose AOC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)

Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch

Lunch Plasma Glucose AOC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)

Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch

Full Information

NCT ID

NCT00747006

First Posted

September 3, 2008

Last Updated

October 21, 2014

Sponsor

Mannkind Corporation

1. Study Identification

Unique Protocol Identification Number

NCT00747006

Brief Title

Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder)When an Optimal Dose is Taken With Varied Carbohydrate Intake

Official Title

A Phase 2, Single-Center, Open-Label, Pharmacodynamic Clinical Trial to Evaluate the Effect of Technosphere® Insulin Inhalation Powder Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder) Safety and Efficacy of Technosphere® Insulin Inhalation Powder (TI Inhalation Powder) on Postprandial Glucose Levels in Subjects With Type 1 and Type 2 Diabetes Mellitus Ingesting Meals With Varied Carbohydrate Content

Study Type

Interventional

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Terminated

Why Stopped

Business reasons

Study Start Date

September 2008 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mannkind Corporation

4. Oversight

5. Study Description

Brief Summary

The purpose of this study is to determine if, once a favorable dose of TI Inhalation Powder is established for either a type 1 or 2 patient, based on a average diabetic meal, the patient's favorable dose can be used safely, regardless of change in meal carbohydrate content. Patients were randomly assigned to various carbohydrate loads (0%, 50%, 100%, 150% or 200%). The 100% carbohydrate load was determined based upon their standard insulin dose for their normal meal.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TI Inhalation Powder (original protocol)

Arm Type

Experimental

Arm Description

Under the original protocol, subjects with Type 1 and Type 2 diabetes will have TI Inhalation Powder administered prandially during dose optimization visits and meal challenge visits (with meals of varying carbohydrate contents). Subjects with Type 2 diabetes will also use TI Inhalation Powder daily at each meal between visits.

Arm Title

TI Inhalation Powder and Humalog (Amendment 1)

Arm Type

Other

Arm Description

Under Amendment 1, TI Inhalation Powder will be administered prandially to a new subset of subjects with Type 2 diabetes during TI dose optimization visits and TI meal challenge visits (with meals of varying carbohydrate contents). Subjects will be crossed over to administration of Humalog 15 minutes before meals during Humalog dose optimization visits and Humalog meal challenge visits (with meals of varying carbohydrate contents). Subjects will also use TI Inhalation Powder daily at each meal between visits.

Intervention Type

Drug

Intervention Name(s)

TI Inhalation Powder and Humalog (Amendment 1)

Intervention Description

Subcutaneous (sc) rapid acting analog to be administered at one half of the meal challenge visits 15 minutes before a meal. Only the last 5 - 10 patients (Type 2) will be undergoing this amendment to the protocol.

Intervention Type

Drug

Intervention Name(s)

TI Inhalation Powder (original protocol)

Intervention Description

Inhaled insulin technology to be administered immediately before a meal (prandially) for glucose control in Type 1 or Type 2 diabetics

Primary Outcome Measure Information:

Title

Lunch Plasma Glucose Time 0 Corrected AUC (0-240) - Original Protocol (TI Treated Type 1 Subjects)

Description

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

Time Frame

0 to 240 minutes

Title

Breakfast Plasma Glucose Time 0 Corrected AUC(0-240) - Original Protocol (TI Treated Type 1 Subjects)

Description

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

Time Frame

0 to 240 minutes

Title

Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)

Description

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

Time Frame

0 to 240 minutes

Title

Lunch Plasma Glucose Time 0 Corrected AUC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)

Description

AUC (area under the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is above time 0 value. AOC (area over the plasma glucose - time curve) from time 0 (immediately before starting meal) to 240 minutes after the start of the meal when the curve is below time 0 value. TIme 0 corrected AUC (0-240) = AUC - AOC

Time Frame

0 to 240 minutes

Title

Lunch Plasma Glucose Excursion - Original Protocol (TI Treated Type 1 Subjects)

Description

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at lunch

Time Frame

0 to 240 minutes

Title

Breakfast Plasma Glucose Excursion - Original Protocol (TI Treated - Type 1 Subjects)

Description

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax - Cmin) at breakfast

Time Frame

0 to 240 minutes

Title

Lunch Plasma Glucose Excursion - Amendment 1 ( TI Treated Type 2 Subjects)

Description

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch

Time Frame

0 to 240 minutes

Title

Lunch Plasma Glucose Excursion - Amendment 1 (Humalog Treated Type 2 Subjects)

Description

Excursion is the difference between plasma glucose Cmax and Cmin (Cmax-Cmin) at lunch

Time Frame

0 to 240 minutes

Secondary Outcome Measure Information:

Title

Lunch Plasma Glucose AOC (0-240) - Original Protocol (TI Treated Type 1 Subjects)

Description

Area over the plasma glucose - time curve from time 0 (immediately before starting lunch) to 240 minutes after the start of the lunch

Time Frame

0 to 240 minutes

Title

Breakfast Plasma Glucose AOC(0-240) - Original Protocol (TI Treated Type 1 Subjects)

Description

Breakfast area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of breakfast

Time Frame

0 to 240 minutes

Title

Lunch Plasma Glucose AOC(0-240) - Amendment 1 (TI Treated Type 2 Subjects)

Description

Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch

Time Frame

0 to 240 minutes

Title

Lunch Plasma Glucose AOC(0-240) - Amendment 1 (Humalog Treated Type 2 Subjects)

Description

Lunch area over the plasma glucose - time curve from time 0 (immediately before breakfast) to 240 minutes after start of lunch

Time Frame

0 to 240 minutes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: Clinical diagnoses of type 1 or type 2 diabetes mellitus Fasting Plasma Glucose (FPG) 80, 140 mg/dL and glycated hemoglobin (A1C) > 6.5% and < or = 10.0%. Body mass index (BMI) of < or = 40 kg/m2 Non-smokers (never smoked or former smokers [= 6 months since cessation]) and a urine cotinine level < or = 100 ng/dL Forced expiratory volume in 1 second (FEV1) = 70% Third National Health and Nutrition Examination Survey (NHANES III) Predicted; pre-bronchodilator FEV1 as a percentage of forced vital capacity (FEV1/Forced vital capacity(FVC)) = 70% For subjects with type 2 diabetes mellitus: Currently receiving oral diabetic treatment or basal insulin +/- oral diabetic treatment Exclusion Criteria: History of chronic obstructive pulmonary disease (COPD), clinically proven asthma, and/or any other clinically important pulmonary disease confirmed by pulmonary function test (PFT) and/or radiologic findings Elevated liver function test (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 times the normal reference range or bilirubin > 1.5 times the reference range) Previous use of Exubera; use of Symlin (pramlintide acetate) and/or Byetta (exenatide) within the past 12 weeks Unstable diabetes control and evidence of severe complications of diabetes mellitus (ie, autonomic neuropathy) Exposure to any investigational product(s) in the past 12 weeks For subjects with type 2 diabetes mellitus: In subjects taking metformin, serum creatinine > 1.4 mg/dL in female subjects and > 1.5 mg/dL in male subjects

Facility Information:

Facility Name

Sansum Medical Research Institute

City

Santa Barbara

State/Province

California

ZIP/Postal Code

93105

Country

United States

Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial